Aging brain最新文献

{"title":"Advanced brain aging mediates the relationship between cardiovascular health and aphasia severity in chronic stroke","authors":"Natalie Busby ,&nbsp;Ida Rangus ,&nbsp;Nicholas Riccardi ,&nbsp;Roger Newman-Norlund ,&nbsp;Chris Rorden ,&nbsp;Julius Fridriksson ,&nbsp;Leonardo Bonilha","doi":"10.1016/j.nbas.2025.100150","DOIUrl":"10.1016/j.nbas.2025.100150","url":null,"abstract":"<div><h3>Introduction</h3><div>There is evidence that overall physical health in general and cardiovascular risk (CV) factors in particular are associated with structural brain changes and recovery trajectories in stroke aphasia, however the nature of these relationships is still unclear. Therefore, we investigated the mediating role of advanced brain aging on the relationship between cardiovascular health and aphasia severity in chronic stroke.</div></div><div><h3>Methods</h3><div>Participants (N = 95) with chronic stroke aphasia completed behavioral testing including the Western Aphasia Battery Aphasia Quotient (WAB AQ) and MRI scanning. Brain age of each participant was calculated using BrainAgeR and their proportional brain age (PBA) was calculated through the relative difference between estimated brain age and chronological age. A CV risk score was also calculated for each participant using the Framingham Heart Study General Cardiovascular Disease Risk Prediction Using BMI calculator. To determine if the relationship between vascular score and WAB AQ is related to brain age, we performed a statistical mediation analysis where the independent variable was vascular score, the dependent variable was WAB AQ and the mediating variable was PBA.</div></div><div><h3>Results</h3><div>Individuals with chronic stroke aphasia who had more cardiovascular risk factors (i.e., a higher vascular score), typically had worse aphasia severity (lower WAB AQ) and advanced brain aging (increased PBA). An increased PBA was also associated with worse aphasia severity. Mediation analyses revealed that individuals with a higher vascular score (i.e., worse heart health) typically had advanced brain aging and, in turn, advanced brain aging was associated with worse aphasia severity. Therefore, the total effect of cardiovascular health on aphasia severity is partially explained by the indirect effects of advanced brain aging.</div></div><div><h3>Discussion</h3><div>Our results corroborate the previous findings suggesting that physical health is an important factor for both brain structural integrity and recovery in stroke aphasia and extends this by demonstrating the mediating effect of advanced brain aging on the relationship between cardiovascular health and aphasia severity. These results highlight the importance of maintaining physical health alongside aphasia therapy and may be an important factor to consider in the long-term management of chronic stroke. Ensuring that individuals have access to resources needed for proper exercise and maintaining a balanced diet may help to improve overall brain structural integrity and therefore may impact aphasia severity.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100150"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau aggregation induces cell death in iPSC-derived neurons","authors":"Hirokazu Tanabe ,&nbsp;Sumihiro Maeda ,&nbsp;Etsuko Sano ,&nbsp;Norio Sakai ,&nbsp;Setsu Endoh-Yamagami ,&nbsp;Hideyuki Okano","doi":"10.1016/j.nbas.2025.100136","DOIUrl":"10.1016/j.nbas.2025.100136","url":null,"abstract":"<div><div>Abnormal accumulation of tau proteins in the brain is a hallmark of neurodegenerative diseases such as Alzheimer’s disease and is closely linked with neuronal cell death. Tau accumulation is a prominent therapeutic target for Alzheimer’s disease, since tau accumulation correlates well with the disease progression, and tau-targeting drugs hold potentials to halt the disease progression. Given the differential response of human and mouse neuronal cells, there is a critical need for a human cellular platform to quickly screen for tau-related neurodegenerative disease therapeutics. However, inducing rapid, tau-dependent neuronal cell death in human models remains challenging. In this study, we established a human cellular model capable of inducing tau aggregation-dependent neuronal cell death within two weeks via tau overexpression. Additionally, we demonstrated the neuroprotective efficacy of known tau-targeting compounds within this system. These findings suggest that our cellular model recapitulates the molecular pathogenesis of tau-induced neurodegeneration and could serve as a valuable platform for drug screening in tauopathies.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal theta oscillations and cognitive flexibility: Age-related modulations in EEG activity","authors":"Margarita Darna ,&nbsp;Christopher Stolz ,&nbsp;Hannah-Sophia Jauch ,&nbsp;Hendrik Strumpf ,&nbsp;Jens-Max Hopf ,&nbsp;Constanze I. Seidenbecher ,&nbsp;Björn H. Schott ,&nbsp;Anni Richter","doi":"10.1016/j.nbas.2025.100142","DOIUrl":"10.1016/j.nbas.2025.100142","url":null,"abstract":"<div><div>Cognitive flexibility, the ability to adapt one’s behaviour in changing environments, declines during aging. Electroencephalography (EEG) studies have implicated midfrontal theta oscillations in attentional set-shifting, a measure of cognitive flexibility. Little is known about the electrocortical underpinnings of set-shifting in aging. Here, we investigated aging effects on set-shifting performance by analysing theta power in 20 young (mean age: 22.5 ± 2.9 years) and 19 older (mean age: 69.4 ± 6.1 years) adults. Increasing shift difficulty (i.e., intra- vs. extra-dimensional shifts) elicited worse performance in both age groups, with older adults showing overall longer reaction times (RTs) and increased RT variability. Young adults exhibited amplified midfrontal theta power increases with higher shift difficulty whereas older adults showed overall lower theta power and no task-related midfrontal theta power modulation, indicating potentially distinct underlying neural mechanisms.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100142"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural stem cell secretome: a secret key to unlocking the power of regeneration in the adult and aging brain","authors":"Soumia Abdellaoui ,&nbsp;Lida Katsimpardi","doi":"10.1016/j.nbas.2025.100144","DOIUrl":"10.1016/j.nbas.2025.100144","url":null,"abstract":"<div><div>Adult neurogenesis involves the activation of quiescent neural stem cells (qNSCs) to generate new neurons, which migrate and integrate into existing neural circuits. In addition to their role in neurogenesis, adult NSCs also secrete bioactive compounds collectively known as the secretome, which contribute to the regulation of this process. However, aging and neurodegenerative diseases impair neurogenesis by promoting a pro-inflammatory environment within the neurogenic niche. With age, NSCs become increasingly quiescent, leading to a decline in their secretory activity— a hallmark of aged NSCs. Enhancing the function of adult NSCs holds therapeutic potential for restoring brain function under these conditions. Specifically, reactivating quiescent NSCs and possibly eliminating senescent ones can boost neurogenesis and improve cognitive function in aging and neurodegenerative diseases. In this review, we explore the role of adult NSCs and their secretome in sustaining brain function throughout adulthood and aging. A comprehensive analysis of the literature sheds light onto how NSCs and their secretome influence neurogenesis, from activation and differentiation to integration into neural circuits. Targeting adult NSCs in aged and neurodegenerative models presents a promising strategy for brain function restoration.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100144"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human adult hippocampal neurogenesis in health and disease","authors":"MC. Alonso-Moreno ,&nbsp;M. Gallardo-Caballero ,&nbsp;AV. Prádanos-Senén ,&nbsp;M. Llorens-Martín","doi":"10.1016/j.nbas.2025.100145","DOIUrl":"10.1016/j.nbas.2025.100145","url":null,"abstract":"<div><div>The mammalian hippocampus generates new dentate granule cells (DGCs) throughout life. This process, named adult hippocampal neurogenesis (AHN), participates in hippocampal functions such as memory and mood regulation. Moreover, AHN is impaired in mouse models and patients with neurodegenerative and psychiatric disorders. Additionally, physiological aging targets AHN and the integrity of the hippocampal neurogenic niche. This perspective review aims to discuss the regulation of human AHN in patients with neurodegenerative and psychistric conditions. Moreover, we will address key adaptations of human AHN and the neurogenic niche in response to physiological aging.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100145"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging","authors":"Robyn A. Honea ,&nbsp;Heather Wilkins ,&nbsp;Suzanne L. Hunt ,&nbsp;Paul J. Kueck ,&nbsp;Jeffrey M. Burns ,&nbsp;Russell H. Swerdlow ,&nbsp;Jill K. Morris","doi":"10.1016/j.nbas.2024.100134","DOIUrl":"10.1016/j.nbas.2024.100134","url":null,"abstract":"<div><div>A growing amount of data has implicated the <em>TOMM40</em> gene in the risk for Alzheimer’s disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of <em>TOMM40</em> rs2075650 (‘650<em>)</em> on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of <em>TOMM40</em> ‘650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of <em>TOMM40</em> ‘650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of <em>APOE</em> ε4. We found that the <em>TOMM40</em> ‘650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that <em>TOMM40</em> ‘650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100134"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins","authors":"Nathan A. Gillespie ,&nbsp;Michael C. Neale ,&nbsp;Matthew S. Panizzon ,&nbsp;Ruth E. McKenzie ,&nbsp;Xin M. Tu ,&nbsp;Hong Xian ,&nbsp;Chandra A. Reynolds ,&nbsp;Michael J. Lyons ,&nbsp;Robert A. Rissman ,&nbsp;Jeremy A. Elman ,&nbsp;Carol Franz ,&nbsp;William S. Kremen","doi":"10.1016/j.nbas.2025.100139","DOIUrl":"10.1016/j.nbas.2025.100139","url":null,"abstract":"<div><div>The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau. No clear evidence that Aβ40 or Aβ42 directly causes t-Tau was observed. Instead, the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL. Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau, though our use of total rather than phosphorylated tau was a limitation. In contrast, Aβ biomarkers appeared to causally impact NFL in cognitively unimpaired men in their late 60 s.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100139"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the association between episodic memory residual reserve index and change in executive function","authors":"Cheyenne Chooi ,&nbsp;Brandon E. Gavett ,&nbsp;David Ames ,&nbsp;Paul Maruff ,&nbsp;Vincent Doré ,&nbsp;Victor L. Villemagne ,&nbsp;Pierrick Bourgeat ,&nbsp;Ying Xia ,&nbsp;Colin L. Masters ,&nbsp;Ralph N. Martins ,&nbsp;Kevin Taddei ,&nbsp;Christopher C. Rowe ,&nbsp;Michael Weinborn ,&nbsp;Stephanie R. Rainey-Smith","doi":"10.1016/j.nbas.2025.100146","DOIUrl":"10.1016/j.nbas.2025.100146","url":null,"abstract":"<div><div>Sex differences in cognitive reserve might contribute to females being disproportionately affected by Alzheimer’s disease (AD). We investigated sex differences in the protective effects of cognitive reserve, and whether brain beta-amyloid accounts for differences. Older adults (n = 997 from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing) diagnosed as Cognitively Normal, Mild Cognitive Impairment, or AD at baseline were assessed every 18 months for up to a maximum of seven visits. Cognitive reserve was calculated from the variance in episodic memory not explained by demographic or brain measures. Executive functioning (EF) intercept and slope were regressed onto the main and interaction effects of cognitive reserve x brain integrity x sex, plus covariates (age, number of <em>APOE</em> ε4 alleles). A three-way interaction was observed between cognitive reserve, brain integrity, and sex on the EF slope. Females benefitted more than males from the protective effects of cognitive reserve at low levels of brain integrity. Sex differences in the protective effect of cognitive reserve were not moderated by brain beta-amyloid burden.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100146"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No sex differences in the association between regional brain structure abnormalities and cognitive functioning in a geriatric memory clinic population","authors":"A. Lamé ,&nbsp;E.G. Thomas ,&nbsp;S.A.J. van de Schraaf ,&nbsp;C. Groot ,&nbsp;C.H. Sudre ,&nbsp;F. Barkhof ,&nbsp;M. Muller ,&nbsp;R. Ossenkoppele ,&nbsp;H.F.M. Rhodius-Meester","doi":"10.1016/j.nbas.2025.100137","DOIUrl":"10.1016/j.nbas.2025.100137","url":null,"abstract":"<div><div>Differences between men and women in cognitive impairment and neurodegeneration are not yet well understood. Although sex differences in brain structure abnormalities, including white matter hyperintensities (WMH) and grey matter (GM) atrophy, have been associated with cognitive decline in the ageing population, the evidence is limited and inconclusive. Therefore, we explored sex differences in brain structure abnormalities and in the association between brain structure abnormalities and cognitive functioning. We analyzed global and regional volumetric measures of WMH and GM of 475 patients visiting an academic geriatric memory clinic in the Netherlands with multiple linear regression analyses. For both global and regional WMH and GM, we found no sex differences in brain structure abnormalities. We also found no interaction of sex on the association between brain structure abnormalities and cognitive functioning. We reflect on using a binary classification of men and women based on sex in this study, which might overlook individual differences and does not elucidate gender-related factors that influence health and risk of pathology. Future studies should focus on exploring the relationship between sex and gender on brain structure and cognitive functioning beyond this binary model, by including more data on social context, more diverse populations and using intersectional approaches.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"7 ","pages":"Article 100137"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of candidate RT-qPCR reference genes in the aging African turquoise killifish brain","authors":"Emily Whisenant,&nbsp;Arne C. Lekven","doi":"10.1016/j.nbas.2025.100151","DOIUrl":"10.1016/j.nbas.2025.100151","url":null,"abstract":"<div><div>Reference genes (RGs) are typically used to normalize gene expression from RT-qPCR experiments. However, the expression of commonly used RGs can vary across different physiological conditions, such as aging, and potentially lead to inaccurate interpretations of results. In African turquoise killifish (<em>Nothobranchius furzeri</em>), the stability of reference genes has not been evaluated during aging. Here, we evaluate six candidate reference genes used in other models of aging (<em>actb</em>, <em>cyc1</em>, <em>gapdh</em>, <em>gusb</em>, <em>oaz1a</em>, and <em>tbp</em>) and examine their brain expression stability in adult males and females from young (10 weeks post-hatching) to old (25 weeks post-hatching). To examine RG stability, we used a combination of summary statistics based on analyses of Cq values, normalized fold change of tyrosine hydroxylase (<em>th</em>), and available computational programs. Overall, we found that <em>cyc1</em>, <em>oaz1a</em>, and <em>gusb</em> were the most stable reference genes during aging across both sexes, with specific rankings reflecting sex-dependent differences, while <em>gapdh</em> and <em>actb</em> were the least reliable. Importantly, when <em>th</em> expression was normalized to our selected RGs, we found that only female samples had an age-related decrease in expression, and expression analysis was highly dependent on the choice of reference gene. Taken together, our findings provide the first systematic evaluation of RG stability in the killifish brain and highlight <em>cyc1</em>, <em>oaz1a</em>, and <em>gusb</em> as reliable RGs for studies of aging. We recommend that future studies use at least two of these RGs in combination for accurate normalization and evaluate RGs for selected experimental conditions within the framework established in this study.</div></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"Article 100151"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}